Delirium
Conditions
Brief summary
The goal of this study is to evaluate the efficacy and safety of suvorexant (MK-4305) for reducing the incidence of delirium in Japanese participants who are at high risk of delirium. The primary hypothesis is that suvorexant reduces the proportion of participants with delirium compared with placebo as assessed by the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria.
Interventions
DRUGSuvorexant
Suvorexant administered at a dose of 15 mg QD via oral tablet
DRUGPlacebo
Suvorexant-matching placebo administered QD via oral tablet
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
65 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* Is hospitalized for (1) acute disease with severe disease state or decreased daily living function or (2) elective surgery requiring general anesthesia scheduled on the day after or 2 days after admission/Day 1 * Has (1) mild cognitive impairment or mild dementia and/or (2) a history of delirium in any prior hospitalization * Requires hospitalization for 6 days for acute disease, with treatment starting on day of admission; or 7 days, with treatment starting the day after admission OR * Requires hospitalization for 6 days for elective surgery scheduled on the day after admission; or for 7 days for elective surgery scheduled 2 days after admission * Is able to take study medications orally
Exclusion criteria
* Has moderate or severe dementia * Has a history of epilepsy or Parkinson's disease * Currently uses psychotropic agents or has a mental condition including schizophrenia, other mental disorders, bipolar disorder and major depression * Has a history of drug or alcohol abuse in the 5 years prior to start of study or has alcoholic disease such as alcoholic liver disease or gastritis alcoholic * Has a history of narcolepsy or cataplexy * Has used hypnotics, antipsychotics, mood stabilizers, antidepressants, anxiolytics, psychostimulants, anticonvulsants or tiapride within 2 weeks prior to randomization * Has delirium as assessed by DSM-5 or DRS-R-98 (total score ≥14.5) before the first dose of study medication
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Delirium as Assessed by Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) Criteria | Up to ~8 days | The DSM-5 is the gold standard for the diagnosis of delirium. DSM-5 criteria were used for clinician assessment of delirium. The percentage of participants with delirium per DSM-5 criteria is presented. |
| Number of Participants Who Experienced One or More Adverse Events (AEs) | Up to ~21 days | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who experienced one or more AEs is presented. |
| Number of Participants Who Discontinued Study Treatment Due to an AE | Up to ~7 days | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who discontinued study treatment due to an AE is presented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Daily Total Score on Delirium Rating Scale-Revised-98 (DRS-R-98) | Up to ~8 days | DRS-R-98 is a diagnostic and assessment tool used for evaluation of delirium. It is a 16-item clinician-rated scale with 13 items measuring delirium severity and 3 diagnostic items. The total DRS-R-98 score can range from 0 (lowest) to 46 (highest). Higher scores indicate worsening or more severe delirium. The maximum daily total score on DRS-R-98 is presented. |
| Percentage of Participants With Delirium as Assessed by DRS-R-98 | Up to ~8 days | DRS-R-98 is a diagnostic and assessment tool used for the evaluation of delirium. It is a 16-item clinician-rated scale with 13 items measuring delirium severity and 3 diagnostic items. The total DRS-R-98 score can range from 0 (lowest) to 46 (highest). Higher scores indicate worsening or more severe delirium. Optimized cutoff score for delirium diagnosis in Japanese-translated DRS-R-98 has been determined as ≥14.5. The percentage of participants with delirium as assessed by DRS-R-98, defined as the percentage of participants with total score ≥14.5 per DRS-R-98, is presented. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Suvorexant Participants received 15 mg of suvorexant orally once daily (QD) for 5 to 7 days. | 105 |
| Placebo Participants will receive suvorexant-matching placebo orally QD for 5 to 7 days. | 102 |
| Total | 207 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 0 |
| Overall Study | One participant canceled surgery and one participant developed delirium before the first dose. | 2 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 0 |
Baseline characteristics
| Characteristic | Placebo | Total | Suvorexant |
|---|---|---|---|
| Age, Continuous | 82.0 Years STANDARD_DEVIATION 4.9 | 81.7 Years STANDARD_DEVIATION 4.6 | 81.5 Years STANDARD_DEVIATION 4.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 102 Participants | 207 Participants | 105 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 102 Participants | 207 Participants | 105 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 57 Participants | 107 Participants | 50 Participants |
| Sex: Female, Male Male | 45 Participants | 100 Participants | 55 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 105 | 0 / 102 |
| other Total, other adverse events | 64 / 101 | 69 / 102 |
| serious Total, serious adverse events | 6 / 101 | 6 / 102 |
Outcome results
Primary
Number of Participants Who Discontinued Study Treatment Due to an AE
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who discontinued study treatment due to an AE is presented.
Time frame: Up to ~7 days
Population: All randomized participants who received at least one dose of study treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Suvorexant | Number of Participants Who Discontinued Study Treatment Due to an AE | 2 Participants |
| Placebo | Number of Participants Who Discontinued Study Treatment Due to an AE | 2 Participants |
95% CI: [-5.1, 5.2]
Primary
Number of Participants Who Experienced One or More Adverse Events (AEs)
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who experienced one or more AEs is presented.
Time frame: Up to ~21 days
Population: All randomized participants who received at least one dose of study treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Suvorexant | Number of Participants Who Experienced One or More Adverse Events (AEs) | 86 Participants |
| Placebo | Number of Participants Who Experienced One or More Adverse Events (AEs) | 86 Participants |
95% CI: [-9.3, 11]
Primary
Percentage of Participants With Delirium as Assessed by Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) Criteria
The DSM-5 is the gold standard for the diagnosis of delirium. DSM-5 criteria were used for clinician assessment of delirium. The percentage of participants with delirium per DSM-5 criteria is presented.
Time frame: Up to ~8 days
Population: All randomized participants who had at least one assessment of delirium by DSM-5 following administration of at least one dose of study treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Suvorexant | Percentage of Participants With Delirium as Assessed by Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) Criteria | 16.8 Percentage of participants |
| Placebo | Percentage of Participants With Delirium as Assessed by Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) Criteria | 26.5 Percentage of participants |
p-value: 0.12995% CI: [-20.1, 2.6]Miettinen and Nurminen method
Secondary
Maximum Daily Total Score on Delirium Rating Scale-Revised-98 (DRS-R-98)
DRS-R-98 is a diagnostic and assessment tool used for evaluation of delirium. It is a 16-item clinician-rated scale with 13 items measuring delirium severity and 3 diagnostic items. The total DRS-R-98 score can range from 0 (lowest) to 46 (highest). Higher scores indicate worsening or more severe delirium. The maximum daily total score on DRS-R-98 is presented.
Time frame: Up to ~8 days
Population: All randomized participants who had at least one assessment of delirium by DSM-5 following administration of at least one dose of study treatment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Suvorexant | Maximum Daily Total Score on Delirium Rating Scale-Revised-98 (DRS-R-98) | 7.0 Score on a scale |
| Placebo | Maximum Daily Total Score on Delirium Rating Scale-Revised-98 (DRS-R-98) | 7.5 Score on a scale |
p-value: 0.48595% CI: [-2, 1]Hodges-Lehmann method
Secondary
Percentage of Participants With Delirium as Assessed by DRS-R-98
DRS-R-98 is a diagnostic and assessment tool used for the evaluation of delirium. It is a 16-item clinician-rated scale with 13 items measuring delirium severity and 3 diagnostic items. The total DRS-R-98 score can range from 0 (lowest) to 46 (highest). Higher scores indicate worsening or more severe delirium. Optimized cutoff score for delirium diagnosis in Japanese-translated DRS-R-98 has been determined as ≥14.5. The percentage of participants with delirium as assessed by DRS-R-98, defined as the percentage of participants with total score ≥14.5 per DRS-R-98, is presented.
Time frame: Up to ~8 days
Population: All randomized participants who had at least one assessment of delirium by DSM-5 following administration of at least one dose of study treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Suvorexant | Percentage of Participants With Delirium as Assessed by DRS-R-98 | 17.8 Percentage of participants |
| Placebo | Percentage of Participants With Delirium as Assessed by DRS-R-98 | 26.5 Percentage of participants |
p-value: 0.13695% CI: [-20.2, 2.8]Miettinen and Nurminen method